Nanoplatform Overcomes Kidney Cancer Drug Resistance
|
By LabMedica International staff writers Posted on 03 Oct 2018 |
|
Image: A micrograph of the most common type of renal cell carcinoma (clear cell)—on right of the image; non-tumor kidney is on the left of the image (Photo courtesy of Wikimedia Commons).
A team of cancer researchers reported the development of a novel "nanoplatform" technology that empowered existing chemotherapeutic drugs to overcome drug-resistance in Everolimus-resistant renal cell carcinoma.
Drug resistance is one of the significant clinical burdens in renal cell carcinoma (RCC). The development of drug resistance has been attributed to many factors, including impairment of apoptosis, elevation of the enzyme carbonic anhydrase IX (CA IX, a marker of tumor hypoxia), and infiltration of tumorigenic immune cells. Everolimus, a derivative of rapamycin, is currently used as an immunosuppressant to prevent rejection of organ transplants and in the treatment of renal cell cancer and other tumors.
To overcome the Everolimus-resistance (Evr-res) that appears in this type of cancer, investigators at Wayne State University (Detroit, MI, USA) used Sorafenib (Sor) - a kinase inhibitor drug approved for the treatment of primary kidney cancer (advanced RCC) - in combination with a novel tumor hypoxia directed nanoparticle (NP) loaded with a new class of apoptosis inducer, CA IX-C4.16. Copper-free "click" chemistry was utilized to conjugate SMA-TPGS (styrene-maleic acid -- D-alpha-tocopheryl polyethylene glycol succinate) with Acetazolamide (ATZ, a CA IX-specific targeting ligand).
The CA IX-SMA-TPGS labeled NPs were designed to selectively deliver their payload to the hypoxic tumor core. The NPs were further tagged with a clinically approved dye for evaluating hypoxic tumor core penetration and organ distribution.
The investigators reported in the August 30, 2018, online edition of the journal Biomaterials that imaging of a tumor spheroid treated with dye-labeled CA IX-SMA-TPGS revealed remarkable tumor core penetration that was modulated by CA IX-mediated targeting in hypoxic-A498 RCC cells. The significant cell killing effect with the synergistic combination of CA IX-C4.16 and Sor treatment suggested efficient reversal of Evr-resistance in A498 cells. Furthermore, treatment with the nanoplatform did not cause liver or kidney toxicity in mice.
“Our tumor hypoxia directed nanoparticle used in conjunction with the FDA-approved renal cell carcinoma treatment, Sorafenib, has had positive outcomes in our animal trials,” said senior author Dr Arun Iyer, assistant professor of pharmaceutical sciences at Wayne State University. “The nanoparticles can deliver the payload selectively to tumor tissue and penetrate deep into the tumor core and provoke significant tumor inhibition with marked safety. This new approach of using our nanoplatform will reopen doors that were once closed because drugs that had become ineffective to cancer treatment are now once again usable and effective. It is our hope that this research will one day soon be used in clinics for treating patients.”
Related Links:
Wayne State University
Drug resistance is one of the significant clinical burdens in renal cell carcinoma (RCC). The development of drug resistance has been attributed to many factors, including impairment of apoptosis, elevation of the enzyme carbonic anhydrase IX (CA IX, a marker of tumor hypoxia), and infiltration of tumorigenic immune cells. Everolimus, a derivative of rapamycin, is currently used as an immunosuppressant to prevent rejection of organ transplants and in the treatment of renal cell cancer and other tumors.
To overcome the Everolimus-resistance (Evr-res) that appears in this type of cancer, investigators at Wayne State University (Detroit, MI, USA) used Sorafenib (Sor) - a kinase inhibitor drug approved for the treatment of primary kidney cancer (advanced RCC) - in combination with a novel tumor hypoxia directed nanoparticle (NP) loaded with a new class of apoptosis inducer, CA IX-C4.16. Copper-free "click" chemistry was utilized to conjugate SMA-TPGS (styrene-maleic acid -- D-alpha-tocopheryl polyethylene glycol succinate) with Acetazolamide (ATZ, a CA IX-specific targeting ligand).
The CA IX-SMA-TPGS labeled NPs were designed to selectively deliver their payload to the hypoxic tumor core. The NPs were further tagged with a clinically approved dye for evaluating hypoxic tumor core penetration and organ distribution.
The investigators reported in the August 30, 2018, online edition of the journal Biomaterials that imaging of a tumor spheroid treated with dye-labeled CA IX-SMA-TPGS revealed remarkable tumor core penetration that was modulated by CA IX-mediated targeting in hypoxic-A498 RCC cells. The significant cell killing effect with the synergistic combination of CA IX-C4.16 and Sor treatment suggested efficient reversal of Evr-resistance in A498 cells. Furthermore, treatment with the nanoplatform did not cause liver or kidney toxicity in mice.
“Our tumor hypoxia directed nanoparticle used in conjunction with the FDA-approved renal cell carcinoma treatment, Sorafenib, has had positive outcomes in our animal trials,” said senior author Dr Arun Iyer, assistant professor of pharmaceutical sciences at Wayne State University. “The nanoparticles can deliver the payload selectively to tumor tissue and penetrate deep into the tumor core and provoke significant tumor inhibition with marked safety. This new approach of using our nanoplatform will reopen doors that were once closed because drugs that had become ineffective to cancer treatment are now once again usable and effective. It is our hope that this research will one day soon be used in clinics for treating patients.”
Related Links:
Wayne State University
Platinum Member
COVID-19 Rapid Test
OSOM COVID-19 Antigen Rapid Test
POCT Fluorescent Immunoassay Analyzer
FIA Go
Gold Member
ADAMTS-13 Protease Activity Test
ATS-13 Activity Assay
Latest BioResearch News
- Genome Analysis Predicts Likelihood of Neurodisability in Oxygen-Deprived Newborns
- Gene Panel Predicts Disease Progession for Patients with B-cell Lymphoma
- New Method Simplifies Preparation of Tumor Genomic DNA Libraries
- New Tool Developed for Diagnosis of Chronic HBV Infection
- Panel of Genetic Loci Accurately Predicts Risk of Developing Gout
- Disrupted TGFB Signaling Linked to Increased Cancer-Related Bacteria
- Gene Fusion Protein Proposed as Prostate Cancer Biomarker
- NIV Test to Diagnose and Monitor Vascular Complications in Diabetes
- Semen Exosome MicroRNA Proves Biomarker for Prostate Cancer
- Genetic Loci Link Plasma Lipid Levels to CVD Risk
- Newly Identified Gene Network Aids in Early Diagnosis of Autism Spectrum Disorder
- Link Confirmed between Living in Poverty and Developing Diseases
- Genomic Study Identifies Kidney Disease Loci in Type I Diabetes Patients
- Liquid Biopsy More Effective for Analyzing Tumor Drug Resistance Mutations
- New Liquid Biopsy Assay Reveals Host-Pathogen Interactions
- Method Developed for Enriching Trophoblast Population in Samples
Channels
Clinical Chemistry
view channel
3D Printed Point-Of-Care Mass Spectrometer Outperforms State-Of-The-Art Models
Mass spectrometry is a precise technique for identifying the chemical components of a sample and has significant potential for monitoring chronic illness health states, such as measuring hormone levels... Read more.jpg "Image: Reaching speeds up to 6,000 RPM, this centrifuge forms the basis for a new type of inexpensive, POC biomedical test (Photo courtesy of Duke University)")
POC Biomedical Test Spins Water Droplet Using Sound Waves for Cancer Detection
Exosomes, tiny cellular bioparticles carrying a specific set of proteins, lipids, and genetic materials, play a crucial role in cell communication and hold promise for non-invasive diagnostics.... Read more
Highly Reliable Cell-Based Assay Enables Accurate Diagnosis of Endocrine Diseases
The conventional methods for measuring free cortisol, the body's stress hormone, from blood or saliva are quite demanding and require sample processing. The most common method, therefore, involves collecting... Read more
Molecular Diagnostics
view channel
Blood Proteins Could Warn of Cancer Seven Years before Diagnosis
Two studies have identified proteins in the blood that could potentially alert individuals to the presence of cancer more than seven years before the disease is clinically diagnosed. Researchers found... Read more (1)_1.jpg "Image: Ultrasound image of micro-histotripsy liberation of biomarkers in a tumor (Photo courtesy of Joy Wang and Pradyumna Kedarisetti)"){kind=small}
Ultrasound-Aided Blood Testing Detects Cancer Biomarkers from Cells
Ultrasound imaging serves as a noninvasive method to locate and monitor cancerous tumors effectively. However, crucial details about the cancer, such as the specific types of cells and genetic mutations... Read more_1.jpg "Image: The innovative method to customize and strengthen DNA origami structure promises breakthroughs in medicine (Photo courtesy of Shutterstock)")
.jpg "Image: The QIAstat-Dx Respiratory Panel Plus has received U.S. FDA clearance (Photo courtesy of QIAGEN)")
Hematology
view channel
Next Generation Instrument Screens for Hemoglobin Disorders in Newborns
Hemoglobinopathies, the most widespread inherited conditions globally, affect about 7% of the population as carriers, with 2.7% of newborns being born with these conditions. The spectrum of clinical manifestations... Read more
First 4-in-1 Nucleic Acid Test for Arbovirus Screening to Reduce Risk of Transfusion-Transmitted Infections
Arboviruses represent an emerging global health threat, exacerbated by climate change and increased international travel that is facilitating their spread across new regions. Chikungunya, dengue, West... Read more
POC Finger-Prick Blood Test Determines Risk of Neutropenic Sepsis in Patients Undergoing Chemotherapy
Neutropenia, a decrease in neutrophils (a type of white blood cell crucial for fighting infections), is a frequent side effect of certain cancer treatments. This condition elevates the risk of infections,... Read more
First Affordable and Rapid Test for Beta Thalassemia Demonstrates 99% Diagnostic Accuracy
Hemoglobin disorders rank as some of the most prevalent monogenic diseases globally. Among various hemoglobin disorders, beta thalassemia, a hereditary blood disorder, affects about 1.5% of the world's... Read moreImmunology
view channel.jpg "Image: The AI predictive model identifies the most potent cancer killing immune cells for use in immunotherapies (Photo courtesy of Shutterstock)")
AI Predicts Tumor-Killing Cells with High Accuracy
Cellular immunotherapy involves extracting immune cells from a patient's tumor, potentially enhancing their cancer-fighting capabilities through engineering, and then expanding and reintroducing them into the body.... Read more
Diagnostic Blood Test for Cellular Rejection after Organ Transplant Could Replace Surgical Biopsies
Transplanted organs constantly face the risk of being rejected by the recipient's immune system which differentiates self from non-self using T cells and B cells. T cells are commonly associated with acute... Read more
AI Tool Precisely Matches Cancer Drugs to Patients Using Information from Each Tumor Cell
Current strategies for matching cancer patients with specific treatments often depend on bulk sequencing of tumor DNA and RNA, which provides an average profile from all cells within a tumor sample.... Read more
Genetic Testing Combined With Personalized Drug Screening On Tumor Samples to Revolutionize Cancer Treatment
Cancer treatment typically adheres to a standard of care—established, statistically validated regimens that are effective for the majority of patients. However, the disease’s inherent variability means... Read moreMicrobiology
view channel
Integrated Solution Ushers New Era of Automated Tuberculosis Testing
Tuberculosis (TB) is responsible for 1.3 million deaths every year, positioning it as one of the top killers globally due to a single infectious agent. In 2022, around 10.6 million people were diagnosed... Read more
Automated Sepsis Test System Enables Rapid Diagnosis for Patients with Severe Bloodstream Infections
Sepsis affects up to 50 million people globally each year, with bacteraemia, formerly known as blood poisoning, being a major cause. In the United States alone, approximately two million individuals are... Read more
Enhanced Rapid Syndromic Molecular Diagnostic Solution Detects Broad Range of Infectious Diseases
GenMark Diagnostics (Carlsbad, CA, USA), a member of the Roche Group (Basel, Switzerland), has rebranded its ePlex® system as the cobas eplex system. This rebranding under the globally renowned cobas name... Read more
Clinical Decision Support Software a Game-Changer in Antimicrobial Resistance Battle
Antimicrobial resistance (AMR) is a serious global public health concern that claims millions of lives every year. It primarily results from the inappropriate and excessive use of antibiotics, which reduces... Read morePathology
view channel
Hyperspectral Dark-Field Microscopy Enables Rapid and Accurate Identification of Cancerous Tissues
Breast cancer remains a major cause of cancer-related mortality among women. Breast-conserving surgery (BCS), also known as lumpectomy, is the removal of the cancerous lump and a small margin of surrounding tissue.... Read more
AI Advancements Enable Leap into 3D Pathology
Human tissue is complex, intricate, and naturally three-dimensional. However, the thin two-dimensional tissue slices commonly used by pathologists to diagnose diseases provide only a limited view of the... Read more
New Blood Test Device Modeled on Leeches to Help Diagnose Malaria
Many individuals have a fear of needles, making the experience of having blood drawn from their arm particularly distressing. An alternative method involves taking blood from the fingertip or earlobe,... Read more
Robotic Blood Drawing Device to Revolutionize Sample Collection for Diagnostic Testing
Blood drawing is performed billions of times each year worldwide, playing a critical role in diagnostic procedures. Despite its importance, clinical laboratories are dealing with significant staff shortages,... Read moreTechnology
view channel
New Diagnostic System Achieves PCR Testing Accuracy
While PCR tests are the gold standard of accuracy for virology testing, they come with limitations such as complexity, the need for skilled lab operators, and longer result times. They also require complex... Read more
DNA Biosensor Enables Early Diagnosis of Cervical Cancer
Molybdenum disulfide (MoS2), recognized for its potential to form two-dimensional nanosheets like graphene, is a material that's increasingly catching the eye of the scientific community.... Read more
Self-Heating Microfluidic Devices Can Detect Diseases in Tiny Blood or Fluid Samples
Microfluidics, which are miniature devices that control the flow of liquids and facilitate chemical reactions, play a key role in disease detection from small samples of blood or other fluids.... Read more
Breakthrough in Diagnostic Technology Could Make On-The-Spot Testing Widely Accessible
Home testing gained significant importance during the COVID-19 pandemic, yet the availability of rapid tests is limited, and most of them can only drive one liquid across the strip, leading to continued... Read moreIndustry
view channel
Danaher and Johns Hopkins University Collaborate to Improve Neurological Diagnosis
Unlike severe traumatic brain injury (TBI), mild TBI often does not show clear correlations with abnormalities detected through head computed tomography (CT) scans. Consequently, there is a pressing need... Read more
Beckman Coulter and MeMed Expand Host Immune Response Diagnostics Partnership
Beckman Coulter Diagnostics (Brea, CA, USA) and MeMed BV (Haifa, Israel) have expanded their host immune response diagnostics partnership. Beckman Coulter is now an authorized distributor of the MeMed... Read more_1.jpg "Image: Thermo Fisher will distribute Bio-Techne products across Europe (Photo courtesy of 123RF)")
